Regulation of cell responses by light controled signal releasing material

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K05843
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: Kyoto University
• Principal Investigator: Sakaguchi Reiko 京都大学, 高等研究院, 特定助教 (80723197)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 細胞応答制御 / ガスバイオロジー / タンパク質工学

Outline of Final Research Achievements

Nitric oxide (NO) functions as a signal molecule in our bodies and has been well studied as vasodilators and regulator of immune systems. However, its precise roles in neuronal system has not been clarified. This research aimed for elucidating the mechanism of nitric oxide production and its downstream roles by utilizing novel material that can release NO by light irradiation. By utilizing lasers for the trigger of NO release, the spatial and temporal resolution could be precisely controlled. Using this material, the effect of NO to neuronal development was investigated in PC 12 cells. The specific exposure to NO resulted in the shrinkage of neuronal axons.
On the other hand, a physical association between an NO-responding Ca2+ channel and nitric oxide synthase via an adaptor protein was discovered. This interaction could be a mechanism to efficiently amplify the Ca2+ and NO production for a positive feedback of the signals.

Free Research Field

生体関連化学

Academic Significance and Societal Importance of the Research Achievements

本研究では、一酸化窒素とその産出酵素が生体内で果たしている役割について明らかにした。生体内でシグナル分子として働いているNOが神経軸索伸長に関与するという知見から、神経変性疾患の発生機構やその治療、進行を抑制する手法の開発に資すると期待される。
また、本研究で見出された、NO産出酵素とCa2+チャネルの機能連関は、生体で血流量の調整を担う血管拡張のメカニズムに光を当て、循環器系疾患の機構の理解に役立つと考えられる。さらに、本研究で開発された、生体内でNO産出をリアルタイムに検出することができるタンパク質ベースセンサーは、診断法への応用が期待される。